Genome screen to detect linkage to common susceptibility genes for intracranial and aortic aneurysms.
OBJECTIVE
Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study.


METHODS
Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite/probable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. Individuals (n=91) were defined as affected if they had an IA (definite/probable) or an aortic or thoracic AA (definite/probable).


RESULTS
Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM; LOD=3.0) and 6 (33 cM; LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively.


CONCLUSIONS
Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.
Worrall
Bradford B
BB
University of Virginia Health System, Department of Neurology, Box 800394, Charlottesville, VA 22908, USA. bbw9r@virginia.edu
Foroud
Tatiana
T
Brown
Robert D
RD
Connolly
E Sander
ES
Hornung
Richard W
RW
Huston
John
J
Kleindorfer
Dawn
D
Koller
Daniel L
DL
Lai
Dongbing
D
Moomaw
Charles J
CJ
Sauerbeck
Laura
L
Woo
Daniel
D
Broderick
Joseph P
JP
D000328:Adult; D000368:Aged; D001014:Aortic Aneurysm / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002874:Chromosome Mapping / Q000379:methods*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D002532:Intracranial Aneurysm / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype